Vasomotor Sympathetic Activity during Early Pregnancy in Humans

描述（由申请人提供）：在美国，妊娠高血压影响了高达10%的孕妇，最严重的先兆子痫是导致孕产妇和胎儿死亡或发病的主要原因。虽然这些并发症的机制尚不清楚，但已经提出妊娠性高血压或子痫前期与高肾上腺素能状态有关，这可能有助于这些疾病的病理生理。交感肾上腺素能控制在人类血压维持中起重要作用。研究发现，在正常妊娠期间，交感神经活动增加，在妊娠晚期患有妊娠性高血压或先兆子痫的妇女中，交感神经活动增加得更多。然而，交感神经亢进是否在正常妊娠早期出现，并在整个妊娠期间保持高水平，或者这种交感神经亢进是否仅在足月发生，从而为妊娠性高血压或子痫前期提供基础，目前尚不清楚。我们发现5名健康的高加索妇女在怀孕早期，交感神经活动非常高（类似于充血性心力衰竭患者），而矛盾的是，她们的血压和外周血管阻力正常。这一发现与关于神经激素适应正常妊娠的普遍观点相反，该观点认为交感神经激活只发生在妊娠后期，据我们所知，在人类妊娠早期没有发表过神经记录。令人惊讶的是，一名亚洲女性在怀孕初期，交感神经活动的增加幅度要小得多，这增加了交感神经活动明显与种族有关的可能性。这些观察结果需要在更多的孕妇中得到验证。因此，本研究项目的目的是确定明显的交感神经激活是否是人类妊娠早期（妊娠8周）的普遍特征，以及交感神经控制在正常妊娠中的作用。为此，该项目的具体目的是检验一种假设，即在健康的白种人而非亚洲妇女的血压正常的情况下，血管舒缩性交感神经活动在怀孕早期急剧增加。这一目标将通过利用微神经摄影的创新技术来实现。如果获得的结果与我们的试点数据相同，它将从根本上改变对妊娠期血压调节的理解，并为妊娠高血压的发展及其最可怕的后果子痫前期提供见解。公共卫生相关性：怀孕期间发生的高血压是母亲和婴儿死亡或发病的一个主要原因，研究发现，交感神经活动的增加与这一问题有关。交感神经活动在保持血压稳定方面起着重要作用。然而，在怀孕后几个月血压正常的孕妇中，交感神经活动也会增加。目前尚不清楚交感神经过度活跃是否在妊娠早期出现，并在整个妊娠期间保持高水平，或者这种交感神经激活是否仅在人类足月发生。这个项目的主要目标就是解决这些问题。获得的结果将为正常妊娠期间，特别是人类早期妊娠期间，交感神经系统如何调节血压提供新的见解。

DESCRIPTION (provided by applicant): Pregnancy-induced hypertension affects up to 10% of pregnant women in the United States, and the most severe form, preeclampsia, is the leading cause of maternal and fetal death or morbidity. Although the mechanisms for such complications are unclear, it has been proposed that either pregnancy-induced hypertension or preeclampsia is associated with a hyperadrenergic state, which may contribute to the pathophysiology of these conditions. Sympathetic adrenergic control plays an important role in blood pressure maintenance in humans. Sympathetic activity was found to increase in normal pregnancy and to be even greater in women with pregnancy-induced hypertension or preeclampsia in late pregnancy. However, it is completely unknown whether sympathetic hyperactivity develops early in normal pregnancy, remaining high throughout the entire gestation, or whether this sympathetic activation only occurs at term, providing the substrate for pregnancy-induced hypertension or preeclampsia. We found in 5 healthy Caucasian women that during early pregnancy, sympathetic activity was extremely high (similar to those of congestive heart failure patients), while paradoxically their blood pressure and peripheral vascular resistance were normal. This finding is counter to the prevailing wisdom regarding the neurohormonal adaptation to normal pregnancy, which suggests that sympathetic activation occurs only in late pregnancy, and to our knowledge, there are no published nerve recordings in early human pregnancy. Surprisingly, one Asian woman in early pregnancy had a much less prominent increase in sympathetic activity, raising the possibility that marked sympathetic activation may be race-dependent. These observations need to be verified in more pregnant women. Thus, the purpose of this research project is to determine whether marked sympathetic activation is a universal characteristic of early pregnancy (d 8 weeks of gestation) in humans and the role of sympathetic neural control in normal pregnancy. To this end, the specific aim of this project will test the hypothesis that vasomotor sympathetic activity increases dramatically during early pregnancy despite a normal blood pressure in healthy Caucasian but not Asian women. This objective will be accomplished by utilizing the innovative technique of microneurography. If the results obtained are the same as in our pilot data, it would radically alter the understanding of how blood pressure is regulated in pregnancy as well as provide insights into the development of gestational hypertension and its most feared outcome, preeclampsia. PUBLIC HEALTH RELEVANCE: High blood pressure occurring during pregnancy is one major cause of death or morbidity for both mothers and babies, and it has been found that an increase in sympathetic activity is related to this problem. Sympathetic activity plays an important role in keeping blood pressure stable. However, increased sympathetic activity was also found in pregnant women whose blood pressure was normal during the latter months of their pregnancies. It is completely unknown whether sympathetic hyperactivity develops early during pregnancy, remaining high throughout the entire gestation, or whether this sympathetic activation only occurs at term in humans. The primary goal of this project is to address these issues. Results obtained will provide novel insights into how blood pressure is regulated by the sympathetic nervous system during normal pregnancy, particularly during early pregnancy in humans.